TUBULAR CHEMOKINE EXPRESSION IN HYDRONEPHROSIS

我们假设趋化因子是在单侧输尿管梗阻模型(UUO)中观察到的白细胞流入和间质纤维化的重要介质。在小鼠UUO中，我们已经鉴定了趋化因子RANTES、MIP-2、IP10和MCP-1的表达。我们建议在这种疾病模型中定位这些趋化因子及其受体的表达。此外，我们打算确定肾素-血管紧张素系统是否诱导趋化因子的表达。这些研究将使用血管紧张素II受体零突变的转基因小鼠和血管紧张素II受体的特异性拮抗剂进行。由于其他研究人员已经确定MCP-1可以诱导成纤维细胞的胶原表达，我们将检测MCP-1是否可以诱导培养的近端肾小管上皮细胞表达胶原。最后，我们的初步证据表明，在UUO大鼠的梗阻肾组织中，树突状细胞浸润。我们建议确定小鼠UUO中的白细胞是否也由树突状细胞组成。

We hypothesize that chemokines are important mediators of the leukocyte influx and interstitial fibrosis observed in the unilateral ureteral obstruction model (UUO) of hydro-nephrosis. In murine UUO, we have identified the expression of the chemokines RANTES, MIP-2, IP10 and MCP-1. We propose to localize the expression of these chemokines and their receptors in this disease model. Furthermore, we intend to determine if the renin-angiotensin system induces chemokine expression. These studies will be performed using transgenic mice that are null mutants for the angiotensin II receptor, and specific antagonists for the angiotensin II receptors. Since other investigators have determined that MCP-1 can induce the expression of collagen from fibroblasts, we will examine if MCP-1 can induce collagen expression from proximal tubular epithelial cells grown in culture. Finally, our preliminary evidence indicates that dendritic cells infiltrate the obstructed kidney in the rat UUO. We propose to determine if the leukocyte infiltrate in murine UUO is also comprised of dendritic cells.